Studies are continuing of the metabolic fate, metabolic interaction and pharmacological activity of several well-known anticonvulsants, several newly synthesized potential anticonvulsants and several other organic compounds of special interest. Specific compounds involved in these investigations are: (1) primidone and its active metabolites (2) phenobarbital and its N-methyl and N,N'-dimethyl derivatives, and the major final metabolites p-hydroxyphenobarbital and its conjugates (3) N,N'-dialkyl-malonamides (4) t-butethal (5) bufotenine, 5-methoxy-DMT, 5-methoxyindole-acetic acid and 5-methoxytryptophol and (6) hexobarbital. Quantitative studies are carried out in vitro and in vivo in mouse and rat, and in vivo in dog and man. Analytical methodology involves solvent extraction, countercurrent distribution, thin layer and gas chromatography. All compounds used are synthesized with suitable 14C label and/or stable isotope label (2H, 13C, 15N) to facilitate quantitation and identification; gas chromatography-mass spectroscopy in the "mass fragmentography" mode is being used for some of the quantitative measurements. Compounds in categories (3) and (4) have been studied for anticonvulsant activity in mice. Hexobarbital metabolism has been investigated in several human subjects. In work carried out in Sweden, bufotenine and 5-methoxydimethyltryptamine have been synthesized with 13C, and 14C labels for metabolism studies in man (which will be carried out in Sweden). Methodology for quantitation of 5-methoxyindole acetic acid and its tryptophol analog in cerebrospinal fluid has been worked out, using the newly synthesized deuterium-labelled compounds and mass-fragmentography. BIBLIOGRAPHIC REFERENCES: Study of the Hepatic Metabolism of Primidone by Improved Methodology. John Alvin, Edward Goh and Milton T. Bush. J. Pharmacol. Exp. Ther. 194, 117-125, 1975. The Metabolism of Triamterene in the Rat. S.T. Kau, B.V. Rama Sastry, J.D. Alvin and M.T. Bush. Drug Metab. and Disp. 3, 345-351, 1975.